SODIUM SELENATE RETARDS EPILEPTOGENESIS VIA ACTIVATING PROTEIN PHOSPHATASE 2A

0001

SODIUM SELENATE RETARDS EPILEPTOGENESIS VIA ACTIVATING PROTEIN PHOSPHATASE 2A

P. Zheng*, S. Liu*, N. Jones*, S. Shultz*, G. Dezsi*, D. Wright†, C. Hovens‡, T.J. O’Brien*,§

*The Royal Melbourne Hospital, Medicine, Melbourne, Australia, †The Florey Institutes of Neuroscience and Mental Health, Melbourne, Australia, ‡The Royal Melbourne Hospital, Surgery, Melbourne, Australia, §Melbourne Brain Centre, Neurology, Melbourne, Australia

Purpose: Epileptogenesis describes the neurobiological processes that convert a healthy brain into an epileptic brain. There are no treatments available to mitigate epileptogenesis in clinical practice. Down-regula- tion of protein phosphatase 2A (PP2A) activity increases phosphorylated tau (p-tau), which is implicated in acquired epilepsy. To investigate the role of PP2A in epileptogenesis, and the effects of a specific PP2A activa- tor – sodium selenate – we utilized three well-characterised rat models of epilepsy: electrical amygdala kindling, post-kainic acid status epilepticus (post-SE) and post-traumatic epilepsy (PTE).

Method: For amygdala kindling, rats were implanted with subcuta- neous osmotic pumps that delivered selenate (1 mg/kg/day) or vehicle continuously for 4 weeks. Rats received 30 electrical stimulations over the final 3 weeks of treatment. For post-SE experiments, SE was induced by kainic acid injections. Rats were then implanted with sub- cutaneous osmotic pumps that continuously released selenate or vehicle for 8 weeks. After 5 weeks of treatment, rats underwent MRI followed by continuous video-EEG monitoring. Rats were then given a drug washout period and then underwent additional video-EEG monitoring. For PTE, rats randomly suffered sham surgery or lateral fluid percus- sion injury and saline vehicle or selenate treatment. After 3-month recovery, all rats underwent video-EEG monitoring during and after the treatment.

Results: PP2A activity and expression of the PR55 regulatory subunit B were significantly decreased, and phosphorylation of tau was increased, in all three models. Selenate treatment slowed the progression of epilep- togenesis in three models (delayed kindling and reduced spontaneous sei- zures post-SE and PTE), reversed the biochemical abnormalities, and reduced hippocampal atrophy in the post-SE model. In post-SE and PTE model, this effect was sustained after drug washout, which indicated an anti-epileptogenic effect.

Conclusion: Epileptogenesis is associated with down-regulation of PP2A activity and an increase in phosphorylated tau, and enhancing PP2A activity with selenate is a potential anti-epileptogenic therapy.

th

– 9 September 2015

Epilepsia, 56(Suppl. 1):3–263, 2015 doi: 10.1111/epi.13241

0002

MORPHOLOGICAL CHANGES IN EEG, AQUAPORIN- 4, C-FOS AND THE HIPPOCAMPUS OF ANIMAL MODELS WITH TEMPORAL LOBE EPILEPSY INDUCED BY KAINIC ACID

E. Taskiran*, C. Yılmaz†, N. Orhan†, M. Bahceci†, M. Kaya‡, B. Ahishali‡, M. Kucuk†, N. Arican‡, C. Gurses§

*Neurology Department, Istanbul Medipol University, Istanbul, Turkey, †Istanbul University, Research Institute of Experimental Medicine, Istanbul, Turkey, ‡Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey, §Department of Neurology and Clinical Neurophysiology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey

Purpose: Temporal lobe epilepsy (TLE) is the most frequent type of localization-related focal epilepsy seen in humans. It has a frequency rate of 30–35% among all epilepsies, and comprises 70% of intractable epilepsies. With hippocampal sclerosis as the most often observed histopathological finding, its epileptogenesis is still researched.

Method: We investigated alterations in EEG findings during epilepto- genesis, and the immunohistochemical correlation of AQP4 and c-fos levels to hippocampal morphology in TLE induced by kainic acid (KA) models. Sixty four young adult (220–270 gr) Wistar albino rats were divided into EEG and immunohistochemistry subgroups of sham, acute and chronic KA groups. Following the implantation of depth electrodes, rats were administered 5–15 mg/kg KA. In addition to observing AQP4 and c-fos proteins at the end of the first 24 hours and 60th day, continu- ous video EEG monitoring (VEM) was carried out for 60 days. Seizure patterns and interictal (II) epileptiform activities on VEM were investi- gated.

Results: All rats in the acute KA group had status epilepticus (SE). While no spontaneous convulsive seizures were observed in the chronic KA group, electrophysiologically rhythmic slow waves were seen during the clinical staring episodes. Interictally, spike/sharp waves were observed. II activity tended to increase gradually during the 60 days. As c-fos immune dying intensified in the hippocampal CA1 and amygdala, an increased rate of AQP4 immune dying in the endotelial cells in the brain capilleries (in the endotelial cells as well as the cytoplasma and feet of the astrocytes) were observed. We determined a correlation between the increased intensity of c-fos and AQP4 proteins in hippocampus and amygdala with the electrophysiological finding of increased number of spikes.

Conclusion: Based on our findings, it is possible to suggest that impaired blood brain barrier (BBB) and increased AQP4 immunoreactivity contibute to the development of epileptogenesis.

3

4

Abstracts

0003

SHARED PATHOPHYSIOLOGY OF TEMPORAL LOBE EPILEPSY AND ALZHEIMER’S DISEASE – A DIFFERENTIAL PROTEOMICS APPROACH IN A POST-STATUS EPILEPTICUS MODEL

E.-L. von Rüden*, C. Zellinger*, A. Walker*, V. Russmann*, K.J. Kleinwort†, C.M. Szober†, C. von Toerne‡, C.A. Deeg†, S.M. Hauck‡, H. Potschka*

*Ludwig-Maximilians-University, Inst. of Pharmacology, Toxicology, and Pharmacy, Munich, Germany, †Ludwig- Maximilians-University, Inst. of Animal Physiology, Munich, Germany, ‡Helmholtz Center Munich, Research Unit Protein Science, Munich, Germany

Introduction: Clinical evidence points to a bidirectional link between temporal lobe epilepsy (TLE) and Alzheimer’s disease (AD). However, clear-cut conclusions about a functional link between the pathophysiolo- gies are clinically difficult. Therefore, we performed a large-scale differ- ential protome analysis in a rat TLE model of epileptogenesis and compared these data sets with available information about differential protein expression in AD models.

Materials and Methods: Following an electrically-induced status epilepticus in female Sprague Dawley rats, hippocampal (HC) and parahippocampal cortex (PHC) tissues were individually subjected to a label-free liquid chromatography tandem mass spectrometry analysis at three time points reflecting the early insult phase (2 days, n = 5), latency phase (10 days, n = 5), and the chronic phase with spontaneous recurrent seizures (8 weeks, n = 5). Control animals (n = 5 per timepoint) were handled in parallel.

Results: We identified proteins associated with amyloid-beta process- ing, deposition, plaque formation, and amyloid-beta-associated pathol- ogy (ApoE and a-synuclein) being regulated in the time course of epileptogenesis.

Moreover, the analysis pointed to an epileptogenesis-associated down-regulation of the microtubule-associated protein Tau in the PHC, whereas Tau exhibited an up-regulation in the HC in the latency phase.

Furthermore, our data sets reveal a prominent dysregulation of mito- chondrial expression patterns, which is a typical feature of AD patho- physiology, in the PHC and a less pronounced dysregulation in the HC associated with epileptogenesis.

Conclusion: Altogether, our findings provide comprehensive informa- tion about the time course of epileptogenesis-associated alterations in the expression patterns of proteins functionally linked with AD pathophysi- ology, pointing towards a shared pathophysiology of both diseases and further providing information about potential biomarkers. These proteins require immunohistological validation in future studies.

We are grateful to Marion Fisch, Sieglinde Fischlein, Fabian Gruhn, Sandra Helm, Barbara Kohler, Regina Rentsch, Claudia Siegl, and Angela Vicidomini for their excellent technical assistance.

0005

SYSTEMIC DELIVERY OF ANTAGOMIRS TARGETING MICRORNA-134 AFTER STATUS EPILEPTICUS REDUCE SPONTANEOUS RECURRENT SEIZURES IN MICE

C. Ruedell Reschke, E.M. Jimenez-Mateos, A. Sanz-Rodriguez, A. Batool, D.C. Henshall

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland

Purpose: Acquired epilepsy is associated with large-scale changes in gene expression which underlie the cell and network-level changes dur- ing epileptogenesis. Despite various efforts we still have no treatments to

Epilepsia, 56(Suppl. 1):3–263, 2015 doi: 10.1111/epi.13241

prevent the emergence of epilepsy following brain injury. Evidence has emerged that microRNAs, a family of small non-coding RNAs, are important regulators of gene expression in epilepsy. Recent work showed that miRNA-134 is overexpressed in the temporal lobe of patients with pharmacoresistant seizures and in experimental models of epilepsy. Silencing miR-134 using intracerebroventricular injections of antago- mirs (Ant) potently suppressed evoked and spontaneous seizures in mice. Here we explored a more clinically relevant route of delivery of these macromolecules, timing injection of antagomirs with blood-brain barrier (BBB) opening after status epilepticus in mice.

Method: Status epilepticus (SE) was induced in C57BL/6 adult mice by an intra-amygdala microinjection of kainic acid. Timing of BBB opening was assessed by Evans blue and FITC-dextran injections, and confirmed by extravasation of serum albumin and mouse IgG levels into the brain parenchyma. Antagomirs were locked nucleic acid- and cholesterol-mod- ified. Injections were then timed accordingly and mice subject to continu- ous long-term video-telemetry EEG recording.

Results: BBB opening in this model was apparent 2 h after status epilep- ticus. Systemic injection of Ant-134 at this time point did not alter the duration or severity of status epilepticus in mice but significantly reduced the number of spontaneous seizures recorded in mice compared with scrambled-sequence and vehicle-injected status epilepticus controls. These seizure-suppressive effects persisted at 1 and 2 months after the SE.

Conclusion: The present study provides evidence that macromolecule targeting of an epilepsy-associated microRNA is effective using a clini- cally-relevant delivery route, supporting the potential translation of this anti-epileptogenic treatment for epilepsy.

Platform Session: Drug Therapy Sunday, 6th September 2015

0006

ASSESSING BIOEQUIVALENCE OF GENERIC MODIFIED RELEASE ANTIEPILEPSY DRUGS

E. Johnson*, Y.-T. Chang†, B. Davit‡, B. Gidal§, G.L. Krauss* *Johns Hopkins School of Medicine, Neurology, Baltimore, MD, USA, †Johns Hopkins University Bloomberg School of Public Health, Biostatistics, Baltimore, MD, USA, ‡Merck Pharmaceuticals, Rahway, NJ, USA, §University of Wisconsin School of Pharmacy, Division of Pharmacy Practice, Madison, WI, USA

Purpose: To determine how closely generic modified-release anti-epi- leptic drugs (MR-AEDs) resemble brand formulations, we compared bioequivalence (BE) data for United States Food and Drug Administra- tion (FDA)-approved MR-AEDs. We compared peak concentrations (Cmax), total absorption (AUC), time to Cmax (Tmax), intersubject vari- ability, and food effects between generic/reference products.

Method: We collected Cmax and AUC data from the BE studies used to support the approvals of 42 generic MR-AED formulations. We com- pared the upper and lower limits of 90% confidence intervals (CI) of the generic/brand AUC and Cmax geometric mean ratios (GMRs), and inter- subject variability, Tmax, and fasting/fed differences for MR formula- tions of: phenytoin (8 products), carbamazepine (5 products), divalproex sodium (7 products), levetiracetam (15 products), and lamotrigine (7 products).

Results: Forty-two MR-AED formulations were studied with 3175 non- epilepsy subjects in 97 fasting or fed BE studies. BE ratios for AUC and Cmax were similar for most products: AUC ratios varied by >15% in 11.4% of BE studies; Cmax varied by >15% in 25.8% of studies. Tmax was more variable, with >30% difference in 13 studies. Tmax was usually

delayed in the fed BE studies compared to fasting studies. Generic and brand products had similar intersubject variability, suggesting either could be used for initial therapy. MR products did not generally reduce intersubject variability in AUC and Cmax compared to immediate release (IR) products; IR and MR lamotrigine provided variable concentrations across subjects while the IR and MR carbamazepine products had less variability.

Conclusion: Most generic and brand MR-AED formulations have simi- lar AUC and Cmax values; a small number of products had 90% CI near acceptance limits which could potentially be clinically significant. Food effects are common with MR-AED products; most MR brand products do not provide advantages with reduced variability across subjects com- pared to generic products or when compared to IR products.

0007

DISEASE-MODIFICATION BY A COMBINATORIAL TREATMENT OF ANTI-INFLAMMATORY DRUGS IN TWO RODENT MODELS OF EPILEPSY

V. Iori, F. Frigerio, A. Pauletti, M. Rizzi, A. Torello, T. Ravizza, A. Vezzani

Mario Negri Institute for Pharmacological Research, Neuroscience, Milan, Italy

Purpose: Neuroinflammation is induced in epileptogenic foci after an inciting event in epilepsy models; this phenomenon was validated in brain specimens from pharmacoresistant patients. Specific anti-inflam- matory treatments greatly reduce provoked or spontaneous seizures in experimental models. We studied whether a combination of drugs target- ing the ictogenic IL-1b/HMGB1 pro-inflammatory signaling affects the disease onset or its progression in two rodent models of symptomatic epi- lepsy.

Method: Status epilepticus (SE) was induced in adult male rodents by electrical stimulation of the hippocampus (Sprague-Dawley rats) or by intra-amygdala injection of kainate (C57BL6 mice). In rats, a combina- tion of anakinra (IL-1 receptor antagonist), BoxA (HMGB1 antagonist) and ifenprodil (NR2B antagonist) was given 1 h post-SE for 6 consecu- tive days. In mice, a combination of VX-765 (IL-1â biosynthesis inhibi- tor) and Cyanobacterial LPS (TLR4 antagonist) was given at the onset of epilepsy for 7 days. Controls were vehicle-injected animals exposed to SE. EEG recording (24/7) was done from SE induction until the onset of spontaneous seizures, and for additional 2 weeks in the chronic epilepsy phases. At the end of recording, the Morris Water Maze or the Novel Object Recognition test was performed to assess cognitive performance, then animals were fixative-perfused for brain histology.

Results: The combined treatments reduced by 2-fold the proportion of animals with a progressive increase in seizure frequency: progression occurred in 40% of treated animals vs 80% in the vehicle group. More- over, the progression index was decreased by 2-fold in treated animals. The treatment reduced by 3-fold seizure frequency in animals with a non- progressive disease. Finally, treatment reduced neurodegeneration in forebrain and improved non-spatial memory deficits in epileptic animals while spatial memory was unaffected.

Conclusion: Pharmacological targeting of IL-1b/HMGB1 signaling either before or after epilepsy onset, specifically interferes with disease progression, suggesting that anti-inflammatory treatments modify the disease course.

Supported by EPITARGET n°602102

0008

PHARMACOLOGICAL OUTCOMES IN JUVENILE MYOCLONIC EPILEPSY OVER 30 YEARS

A. Chowdhury, M.J. Brodie

Western Infirmary, Epilepsy Unit, Glasgow, UK

Purpose: To investigate the long-term outcomes in patients with Juve- nile Myoclonic Epilepsy (JME) at a single centre over 30 years.

Method: A retrospective analysis was undertaken in 186 patients (male: n = 78; female: n = 108) diagnosed with JME at the Epilepsy Unit in the Western Infirmary, Glasgow, Scotland between July 1982 and 2012.

Results: Median age at treatment start was 16 years (range 12–44 years) with a median duration of follow-up of 14 years (range 2–32 years). Overall 171 patients (92%) achieved terminal remission on antiepileptic drug (AED) therapy with a mean seizure-free period of 9.5 years (range 1–31 years). Fifteen patients (5 male, 10 female) continued to have sei- zures despite taking up to 8 AED regimens, 7 of whom had psychiatric comorbidities. Most commonly prescribed AEDs included sodium val- proate (VPA; n = 142), lamotrigine (LTG; n = 66) and levetiracetam (LEV; n = 22). Overall, VPA represented 44% of all AEDs prescribed to male patients compared with 31% in females. Fewer males received LTG (n = 17;26%vs.n = 49;74%)andLEV(n = 4;18%vs.n = 18;82%). Terminal remission was achieved more often using monotherapy with VPA(n=74,52%)andLEV(n=12,55%)thanwithLTG(n=21; 32%). More males than females attained terminal remission on their first or second AED (n = 69; 88% vs. n = 60; 56%). AED monotherapy resulted in intolerable side-effects in 76 patients.

Conclusion: JME is a benign syndrome with high rates of seizure free- dom. Female patients had a worse outcome than males, since they were less likely to receive VPA because of concerns regarding teratogenicity. Patients with psychiatric comorbidities were also less likely to achieve optimal seizure control.

0009

EFFICACY AND SAFETY OF ANTI-TUMOR NECROSIS FACTOR ALPHA THERAPY IN RASMUSSEN’S ENCEPHALITIS: AN OPEN STUDY

S. Lagarde*,†, N. Villeneuve‡,§, F. Bartolomei*,†, Adalimumab Rasmussen Study Group

*Assistance Publique-Ho^pitaux de Marseille, H^opital de la Timone, Service de Neurophysiologie Clinique, Marseille, France, †Aix Marseille Université, Institut de Neurosciences des Syst􏰀emes, Marseille, France, ‡H^opital Henri Gastaut, Marseille, France, §Assistance Publique-H^opitaux de Marseille, H^opital de la Timone, Service de Neuropédiatrie, Marseille, France

Purpose: Rasmussen’s encephalitis (RE) is a severe chronic inflamma- tory brain disorder affecting one cerebral hemisphere, leading to drug- resistant epilepsy, progressive neurological deficit and unilateral brain atrophy. Some immunomodulatory therapies have been tried with varied efficacy, but there is no standardized treatment strategy. TNF a seems to play an important role in RE pathophysiology including pro-inflamma- tory, pro-epileptogenic and pro-excitotoxicity effects.

Method: We report an open study evaluating the effect of anti-TNF-a therapy (Adalimumab) in 10 patients with RE. The main outcome crite- rion was the decrease by 50% of monthly number of days with seizure.

Results: Adalimumab was started with a median delay of 4.8 years after first seizures (range: 1 month-16 years) and followed-up a median per- iod after initiation of 18.4 months (range: 12–36 months). Four patients (40%) were found to be responders experiencing a rapid and prolonged effect after Adalimumab initiation. Adalimumab was well tolerated with- out remarkable clinical side effects.

Conclusion: Adalimumab showed safety of use and efficacy in a propor- tion of patients with RE, in term of seizure control and neurological defi- cit. The long-term effect of this treatment on larger series is needed to confirm these preliminary promising results.

Epilepsia, 56(Suppl. 1):3–263, 2015 doi: 10.1111/epi.13241

5

Abstracts

6

Abstracts

0010

SPASM CONTROL AT 3, 6 AND 12 MONTHS IN WEST SYNDROME: RANDOMISED, SINGLE BLIND CLINICAL TRIAL ON INTRAMUSCULAR LONG ACTING ACTH VERSUS ORAL PREDNISOLONE

J. Wanigasinghe*, C. Arambepola*, S. Sri Ranganathan*,

S. Sumanasena†, E. Muhandirum*

*University of Colombo, Colombo, Sri Lanka, †University of Kelaniya, Colombo, Sri Lanka

Purpose: Most literature on treatment for West syndrome, concentrate on the immediate spasm control. What is important is to identify the long term outcome in relation to spasm control and developmental outcome. Hormonal therapy is currently established as its first line therapy. However, which form of hormonal therapy i.e. intra-muscular long acting tetracosactrine (ACTH) or oral prednisolone is more efficacious for long term spasm control is not yet known.

Method: A prospective randomized, single blind clinical trial was con- ducted in Sri Lanka. Ninety seven newly diagnosed, previously untreated children with confirmed epileptic spasms, with hypsarrhythmia on EEG, were randomized to receive oral prednisolone or ACTH for 14 days according to the United Kingdom Infantile Spasm Study protocol. Spasm control was evaluated at different time points (3, 6, and 12 months). Spasm control was defined as absence of spasms for more than 1 week at these reviews.

Results: Forty eight infants on prednisolone and 49 on ACTH completed the treatment. Spasm cessation by 14th day occurred in 58.3% with pred- nisolone in comparison to only 36.7% with ACTH (p = 0.03). The num- ber of children completing follow up at 6 and 12 months were 29 and 29 for prednisolone and 23 and 25 for ACTH respectively. There were 3 deaths by 6 months and 6 deaths by 12 months. Absence of spasms at 3rd-month follow up was 66.7% with prednisolone and 38.2% with ACTH (p = 0.006). Absence of spasms at 6 months with prednisolone was 60.4% compared to 46.9% with ACTH (p = 0.18). Absence of spasms at 12 months was 60.4% for prednisolone and 51% for ACTH (p = 0.35).

Conclusion: This trial shows that the spasm control for first 3 months was significantly better if treated with oral prednisolone. However, long- term spasm control at 6 and 12 months was similar for oral prednisolone and intramuscular ACTH.

Platform Session: Epilepsy Surgery 1 Sunday, 6th September 2015

0011

HIGH FREQUENCY OSCILLATIONS IN THE INTRA- OPERATIVE CORTICOGRAM BEFORE AND AFTER SURGERY: BETTER PREDICTION OF OUTCOME

M. van ‘t Klooster*, N. van Klink*, W. Zweiphenning*,

F. Leijten*, R. Zelmann†, C. Ferrier*, P. van Rijen*, K. Braun*, G. Huiskamp*, M. Zijlmans*,‡

*Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands, †Montreal Neurological Institute, McGill University, Montreal, Canada, ‡SEIN, Stichting Epilepsie Instellingen Nederland, Heemstede, Netherlands

Purpose: The aim of intra-operative electrocorticography (ECoG) is delineation of epileptogenic tissue for complete resection. This tailoring currently relies on interpretation of interictal spikes. High frequency oscillations (HFOs, ripples 80–250 Hz, especially fast ripples (FRs, 250– 500 Hz), are considered a better biomarker for epileptogenic tissue than

Epilepsia, 56(Suppl. 1):3–263, 2015 doi: 10.1111/epi.13241

spikes. We studied the predictive value of HFOs versus spikes in com- bined pre- and post-resection ECoG for surgical outcome.

Method: We studied pre- and post-resection ECoG recorded at 2048 Hz in patients with refractory focal epilepsy. We marked FRs, ripples and spikes in 1 minute of each recording. We determined presence (+) or absence (-) of these events pre- and post- resection and defined four patient groups: pre+post- (+/-), pre+post+ (+/+), pre-post+ (-/+) and pre- post- (-/-). We compared residual post-resection events to outcome, given the presence or absence of pre-events (Fisher exact). Outcome was cate- gorized into seizure freedom (Engel 1A) vs. seizure recurrence (Engel 1B-4).

Results: We included 54 patients (median age 15.5y, 33 TLE) with 25 months median follow-up. Twenty-four patients had recurrent sei- zures. The number of patients with FRs[+/-,+/+,-/+,-/-] were [28,10,2,14], with ripples [3,51,0,0] and with spikes [12,34,4,4]. Residual FRs, given the presence of pre-resection FRs(+/-,+/+) were significantly associated with outcome (p = 0.02): eighteen out of twenty-eight patients with FRs before but not after resection were seizure-free and eight out of ten patients with FRs before and after resection had seizure recurrence. Presence or absence of residual FRs had no predictive value in the absence of pre-resection FRs(-/+,-/-) (p = 1.0). There was no asso- ciation with outcome for ripples (p(+/-,+/+)=0.25) and spikes (p(+/- ,+/+)=0.74, p(-/+,-/-)=1.0).

Conclusion: The presence or absence of FRs in post-ECoG, given FRs in pre-ECoG is a prognostic marker for surgical outcome. The use of FRs for tailoring with repeated ECoG recordings might influence the success rate of epilepsy surgery in individual cases.

0012

LONG TERM OUTCOME OF PATIENTS WITH OCCURRENCE OF SEIZURES IN FIRST YEAR AFTER EPILEPSY SURGERY

M. Ryzí*, H. O􏰁slej􏰁skov􏰂a*, M. Br􏰂azdil†, Z. Nov􏰂ak‡,

J. Chrastina‡, I. Rektor†

*Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, †Epilepsy Center Brno; First Department of Neurology, St. Anne’s University Hospital and Faculty of Medicine, Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic, ‡Epilepsy Center Brno; Department of Neurosurgery, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic

Purpose: The aim of the study was to evaluate the long term outcome of patients with persisting seizures in first year after epilepsy surgery. The secondary objectives were to analyse

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